1. Field of the Invention
The apparatus and methods disclosed herein relate to the preparation of sterile water for various medical uses. An exemplary medical use is the preparation of peritoneal dialysate solutions or hydration fluids under sub-optimal conditions.
2. Description of the Related Art
The preparation of medicaments in the field or under sub-optimal conditions is complicated by the absence of clean water supplies. Existing water purification devices that produce pharmaceutical grade water (PGW) in remote locations have limited production capacity, both by limiting flow rates and by reducing product life span. The purification capacity of such devices can become severely limited when used to purify significantly contaminated water sources. In fact, even potable water quality standards for municipal water treatment throughout the developed world allow widely variable levels of contamination that render such water supplies unsuitable for use in the preparation of medicaments, without further purification.
Effective water purification to a level that meets pharmaceutical-grade water (PGW) quality standards typically requires extensive mechanical, filtration, chemical, and other forms of manipulation. Disinfection alone is not adequate to achieve PGW. Elevated levels of dissociable ions are acceptable in municipally treated waters for drinking but are potentially hazardous to health if administered in non-physiologic levels. The by-products of microbial contamination even following Disinfection are potentially life threatening. Endotoxins derived from gram negative bacteria represent a life threatening hazard resulting from pyrogenic shock. A number of common water contaminants are discussed below.
Particulate Contamination
PGW have limits that do not apply to potable water standards maximal potable water standards for particulate matter severely limits the capacity of remote site PGW purification systems.
Organics Contamination
The acceptable levels of organic contaminants in drinking water may exceed acceptable levels in a therapeutic PGW due to the potential toxicity of intravenous administration of these agents. The toxicology associated with ingested agents is a function of the blood level reached following absorption into the blood stream. With therapeutic solutions produced from PGW, the amount of organic contaminants associated with the PGW is the blood level. Therefore, exhaustive purification beyond drinking water quality is necessary to mitigate the potential toxicity. This problem is exacerbated with the use of available water with uncontrolled organic contamination. Without preliminary removal of organic contaminants, a PGW system would have severely reduced purification capacity.
Deionization
Dissolved solids constitute a significant contaminant in water. These agents include salts, most commonly in the form of sodium chloride. Dissolved solids also include inorganic contaminants including heavy metals, such as arsenic, mercury, lead, and iron. As with removal of organic contaminants, the toxicology of these agents is markedly increased with direct administration into the blood stream. The deionization capacity of a PGW system would be markedly limited without preliminary deionization of the source water.
Disinfection
Perhaps the greatest acute hazard to ingestion of available water results from the potentially infectious agents that may be present therein. The most effective preventative measure to combat this hazard involves the disinfection of the source water.
Among the potentially infectious agents that must be removed from source water include viruses, bacteriological agents, spore-forming parasites, and fungal agents. The larger of these agents are readily filtered from source water. Some microbial agents, however, have the capacity to grow through filters, thus rendering them non-sterile. Moreover, viruses pass through microfilters, therefore requiring the use of ultrafilters or reverse osmosis filtration. These forms of filtration require expansive mechanical generation of high pressure and thus entail an extensive power requirement.
Drinking water disinfection devices are capable of rendering viruses and microbes inactive and non-replicative. These devices, however, do not remove these agents or cell debris from the product water. In situations where the water is intended for drinking, the point is not of great importance because generally viruses, bacteria, bacterial by-products, spores, or other microbiological materials if killed or rendered non-replicative, do not represent potential hazards.
For production of water-based, injectable fluids, bacterial-by products represent a significant hazard and must be removed to prevent pyrogenic shock and potential death. The purification capacity of PGW systems is limited, without a preliminary filtration of these agents in combination with a Disinfection step, which renders the microbial agents non-replicative.